3 replies to this topic

[Hyperflux]

Does anyone have any experience on insight with using dopamine agonists for depression and anhedonia such as cabergoline (Dostinex) or pramipexole (Mirapex)? Here's a good guide showing the efficacy of Pramipexole for TRD/anhedonia (also see the video by Dr. Fawcett).

 

How would cabergoline (Dostinex) compare to pramipexole (Mirapex) for TRD and anhedonia? They're both potent dopamine agonists. Caber is touted to be the most efficacious dopamine agonist therapeutically with the least side effects (most people online prefer it over prami but they use it for body composition and sexual enhancement purposes and I think).

 

Caber is a potent D2 agonist and weak D1 agonist.

Prami is a moderate D2, D3 and D4 agonist but with stronger D3 agonism. I was under the impression that D2 agonism is the most important site receptor for mood and motivation related disorders while D4 is more responsible for executive functioning (ADHD). Not sure how D3 and D1 agonism comes into play.

 

Also, is it worth trying caber or prami if one tried l-dopa in the past (180 mg l-dopa daily for a month from mucuna pruriens)? I couldn't sleep on it and I got DAWS symptoms upon discontinuation.

[Mind_Paralysis]

I don't consider them worth trying.

 

The results are imho, not conclusive enough, and the discontinuation-symptoms and side-effects can be problematic.

 

Pramipexole in particular is problematic - its D3 agonism causes hypersexuality and impulsive behaviour - mania, gambling, addiction, cheating, spending, et c.

 

 

There's also the fact that there can be a great deal of tolerance from these types of direct agonists - it's a well-known problem that most dopamine-receptors are NOT fond of getting constant strong signalling, and will hence down-regulate very powerfully.

 

(the D4-receptor is interestingly enough the only D-receptor which seems to be resilient towards both up and down -regulation, which lends credence to the observations that the therapeutic effects on ADHD-symptoms are the effects which reach tolerance the slowest - as such, it's quite possible that many whom take stimulants therapeutically are fooling themselves when they claim that they have developed tolerance quickly - it's the OTHER effects which they enjoyed that have lessened - not the effects on ADHD.)

 

 

I'd suggest instead looking into Selegiline if you want to go the dopamine-route - a dopamine-selective MAOI - it has fairly good evidence for effectiveness in the treatment of depression.

 

 

And, as always... since TRD can be caused by undiagnosed neuropsychiatric and neurodevelopmental disorders, I must ask if this is something that you and your Dr's have looked into? Things like:

 

Autism

ADHD

SCT (ADHD-NOS, ADHD-PI, etc...)

*BIPOLAR NOS*

 

NOS = Not Otherwise Specified.

 

Atypical Bipolar in particular, is known to be a big cause of TRD - there are many, many forms of the disorder it would appear, and the classical BP1 and BP2 classifications are more or less considered faulty these days.

 

If you haven't looked into these things, then you definitively need to do so.

 

 

Refs:

EMSAM (deprenyl patch): how a promising antidepressant was underutilized

https://www.ncbi.nlm...les/PMC4200016/

(note the effects on atypical depression - it's not uncommon for TRD to be caused by atypical not getting the right treatment)

 

 

A closer look at treatment resistant depression: is it due to a bipolar diathesis?

https://www.ncbi.nlm...pubmed/15708423

 

Bipolar mood disorder and treatment-resistant depression

https://www.ncbi.nlm...les/PMC2991825/

 

Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?

https://www.ncbi.nlm...pubmed/20655113

 

(my goal with the above studies is not to say that all people with TRD have BD, but that it's a definitive factor that needs to be looked into, with every patient. Hence, it's something you need to look into as well - specifically the SPECTRUM-model of BD - remember... there are many forms of the disorder.)

[Hyperflux]

I don't consider them worth trying.

 

The results are imho, not conclusive enough, and the discontinuation-symptoms and side-effects can be problematic.

 

Pramipexole in particular is problematic - its D3 agonism causes hypersexuality and impulsive behaviour - mania, gambling, addiction, cheating, spending, et c.

 

 

There's also the fact that there can be a great deal of tolerance from these types of direct agonists - it's a well-known problem that most dopamine-receptors are NOT fond of getting constant strong signalling, and will hence down-regulate very powerfully.

 

(the D4-receptor is interestingly enough the only D-receptor which seems to be resilient towards both up and down -regulation, which lends credence to the observations that the therapeutic effects on ADHD-symptoms are the effects which reach tolerance the slowest - as such, it's quite possible that many whom take stimulants therapeutically are fooling themselves when they claim that they have developed tolerance quickly - it's the OTHER effects which they enjoyed that have lessened - not the effects on ADHD.)

 

 

I'd suggest instead looking into Selegiline if you want to go the dopamine-route - a dopamine-selective MAOI - it has fairly good evidence for effectiveness in the treatment of depression.

 

 

And, as always... since TRD can be caused by undiagnosed neuropsychiatric and neurodevelopmental disorders, I must ask if this is something that you and your Dr's have looked into? Things like:

 

Autism

ADHD

SCT (ADHD-NOS, ADHD-PI, etc...)

*BIPOLAR NOS*

 

NOS = Not Otherwise Specified.

 

Atypical Bipolar in particular, is known to be a big cause of TRD - there are many, many forms of the disorder it would appear, and the classical BP1 and BP2 classifications are more or less considered faulty these days.

 

If you haven't looked into these things, then you definitively need to do so.

 

 

Refs:

EMSAM (deprenyl patch): how a promising antidepressant was underutilized

https://www.ncbi.nlm...les/PMC4200016/

(note the effects on atypical depression - it's not uncommon for TRD to be caused by atypical not getting the right treatment)

 

 

A closer look at treatment resistant depression: is it due to a bipolar diathesis?

https://www.ncbi.nlm...pubmed/15708423

 

Bipolar mood disorder and treatment-resistant depression

https://www.ncbi.nlm...les/PMC2991825/

 

Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?

https://www.ncbi.nlm...pubmed/20655113

 

(my goal with the above studies is not to say that all people with TRD have BD, but that it's a definitive factor that needs to be looked into, with every patient. Hence, it's something you need to look into as well - specifically the SPECTRUM-model of BD - remember... there are many forms of the disorder.)

 

DAWS is definitely worrisome. I think it might be worth a try as a last resort but otherwise not worth it. 

[John250]

I used Pfizer cabergoline at .5mg 2x per week for 7 years straight when I was a competitive bodybuilder to keep prolactin levels down from using HGH in higher doses. From 2006-2013. Prolactin blood tests were <0. At the time I figured it was fine I figured it was just like using an anti-estrogen but for prolactin I wasn’t aware it could have long-term side effects. I abruptly stopped and did not feel or notice any side effects. No changes in mood nothing. The only thing that was odd was my prolactin stayed at <0 for like 3-4 months after discontinuing it but then it went back to normal levels.